The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

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by Jessica Wapner
     
 

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Philadelphia, 1959: A scientist scrutinizing a single human cell under a microscope detects a missing piece of DNA. That scientist, David Hungerford, had no way of knowing that he had stumbled upon the starting point of modern cancer research— the Philadelphia chromosome. It would take doctors and researchers around the world more than three decades to

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Overview

Philadelphia, 1959: A scientist scrutinizing a single human cell under a microscope detects a missing piece of DNA. That scientist, David Hungerford, had no way of knowing that he had stumbled upon the starting point of modern cancer research— the Philadelphia chromosome. It would take doctors and researchers around the world more than three decades to unravel the implications of this landmark discovery. In 1990, the Philadelphia chromosome was recognized as the sole cause of a deadly blood cancer, chronic myeloid leukemia, or CML. Cancer research would never be the same.

Science journalist Jessica Wapner reconstructs more than forty years of crucial breakthroughs, clearly explains the science behind them, and pays tribute—with extensive original reporting, including more than thirty-five interviews—to the dozens of researchers, doctors, and patients with a direct role in this inspirational story. Their curiosity and determination would ultimately lead to a lifesaving treatment unlike anything before it.

The Philadelphia Chromosome chronicles the remarkable change of fortune for the more than 70,000 people worldwide who are diagnosed with CML each year. It is a celebration of a rare triumph in the battle against cancer and a blueprint for future research, as doctors and scientists race to uncover and treat the genetic roots of a wide range of cancers.

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Editorial Reviews

The Wall Street Journal
“In [The Philadelphia Chromosome], Jessica Wapner chronicles the ensuing decades of laborious scientific inquiry and industrial ingenuity that led to the discovery of Gleevec, the first drug designed to attack cancer at the genetic level. Its success in beating CML into remission and making the errant chromosome disappear has helped to revolutionize cancer research, unleashing a hunt for the genetic basis of other cancers and opening the door to comparable targeted treatments.”
The Wall Street Journal
The New York Times
“Among a small cluster of very good recent books on cancer.”
The New York Times
The Washington Post
“This reporting takes in a huge swath of science and research, a landscape that changes dramatically over the course of her story. Wapner’s achievement is to help the reader understand why each development is huge in its time and place—starting with Hungerford peering through his camera at the chromosomes and following scientists through the laboratory stories, through drug development and animal testing, to the triumphant patient treatment when the drug becomes almost routine—a scientific miracle absorbed into the daily lives of a group of patients no longer united by a fatal diagnosis.”
The Washington Post
American Scholar
“[A] riveting suspense story . . . Ten years ago, CML was a death sentence. Today, with Gleevec, most of its sufferers lead full and normal lives. Wapner tells the complex story of how this came to be with clarity, eloquence, and balanced insight.”
American Scholar
Nature
“A crucial link between genetics and cancer emerged in a US lab in 1959, as researcher David Hungerford peered down a microscope at an abnormally small chromosome. In 1990, this ‘Philadelphia chromosome’ was found to cause the swiftly fatal chronic myeloid leukaemia. As science writer Jessica Wapner reveals in this taut, elegant study, a cascade of breakthroughs then led to success with targeted drug Gleevec, a tyrosine kinase inhibitor—and hopes for the cancer-busting potential of rational drug design in general.”
Nature
The Scientist
“[T]he way Wapner repeatedly adds up preceding steps to build to the scientific breakthrough is masterful, making for compulsive, surprisingly emotional reading."
The Scientist
Science
“A thriller with a dash of history.”—Science
The Barns & Noble Review
“Expounding the well-known link between genetics and cancer, this scientific history recounts the initial discovery of a gene mutation that eventually led to enormous breakthroughs in the fight against leukemia.”
The Barnes & Noble Review
Shelf Awareness
“Jessica Wapner reveals how the discovery of a single mutated chromosome led to a trailblazing treatment for leukemia and a variety of other cancers.”
Shelf Awareness
Philadelphia Weekly
“Splendidly written in the tradition of the legendary medical book, Microbe Hunters, this book proves that medical science is as cool as those forensic shows like CSI.”
Philadelphia Weekly
Nature Medicine
“I would enthusiastically recommend [this book] to the lay public, people living with cancer and cancer researchers. . . .[T]he story of the Philadelphia chromosome—the scientific creativity and the dedication it celebrates and the medical scientific triumph it represents—is one that deserves to be cherished for eternity.”
Nature Medicine
Philadelphia Inquirer
“[The Philadelphia Chromosome] opens our eyes to a future in which remedies will kill tumors at their root.”
—Philadelphia Inquirer
New York Post
“[C]hronicles the decades-long quest to develop a targeted, or ‘rational,’ treatment that would attack cancer on the genetic level.”
New York Post
Helen Lawce
“I enjoyed the book immensely for its enthusiasm, compassion, and depth, while remaining accessible to those not versed in science. It should become a classic.”
Helen Lawce, Journal of the Association of Genetic Technologists
Siddhartha Mukherjee
“The story of the Philadelphia chromosome is truly the story of modern cancer biology—from the very earliest description of a chromosomal abnormality in cancer cells to the development of a targeted medicine against a formerly lethal type of leukemia. Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
Siddhartha Mukherjee, Pulitzer Prize–winning author of The Emperor of All Maladies
David B. Agus
“Jessica Wapner shows us in The Philadelphia Chromosome how the past and the future combine to dramatically change the course of a disease. This beautifully written book is a blueprint for broader healthcare change. A pivotal book.”
David B. Agus, MD, Professor of Medicine and Engineering, University of Southern California, and author of The End of Illness
David Quammen
“Jessica Wapner has done two kinds of hard work gracefully: the hard work of understanding cancer genetics and the hard work of rendering that subject into human narrative, lucid explanation, and metaphor. The Philadelphia Chromosome is not just an urgently useful book. It's also an elegant one, put together like a Swiss watch.”
David Quammen, author of Spillover: Animal Infections and the Next Human Pandemic
Seth Mnookin
“The Philadelphia Chromosome clearly explains how a half-century’s worth of research transformed a viciously lethal form of cancer into a chronic, treatable condition. Jessica Wapner’s meticulously researched book is both a real-life medical thriller and an engaging narrative about the history of modern cancer research.”
Seth Mnookin, author of The Panic Virus: The True Story Behind the Vaccine-Autism Controversy
From the Publisher
One of The Wall Street Journal's 10 Best Nonfiction Books of 2013:
“There were numerous strong books about cancer in 2013, but this account of the decades of work to find a drug to fight chronic myelogenous leukemia was the strongest. Jessica Wapner translates the complexities of medical science for the general reader and demonstrates the necessity of collaboration between two traditional enemies, academia and Big Pharma.”

“Among a small cluster of very good recent books on cancer.”
The New York Times

“This reporting takes in a huge swath of science and research, a landscape that changes dramatically over the course of her story. Wapner’s achievement is to help the reader understand why each development is huge in its time and place—starting with Hungerford peering through his camera at the chromosomes and following scientists through the laboratory stories, through drug development and animal testing, to the triumphant patient treatment when the drug becomes almost routine—a scientific miracle absorbed into the daily lives of a group of patients no longer united by a fatal diagnosis.”
The Washington Post

“In [The Philadelphia Chromosome], Jessica Wapner chronicles the ensuing decades of laborious scientific inquiry and industrial ingenuity that led to the discovery of Gleevec, the first drug designed to attack cancer at the genetic level. Its success in beating CML into remission and making the errant chromosome disappear has helped to revolutionize cancer research, unleashing a hunt for the genetic basis of other cancers and opening the door to comparable targeted treatments.”
The Wall Street Journal

“[A]riveting suspense story . . . Ten years ago, CML was a death sentence. Today, with Gleevec, most of its sufferers lead full and normal lives. Wapner tells the complex story of how this came to be with clarity, eloquence, and balanced insight.”
American Scholar

“An excellent book for those who want to learn more about how medical discoveries are made and those interested in recent medical history, as well as those whose lives are affected by CML.”
Library Journal

“A crucial link between genetics and cancer emerged in a US lab in 1959, as researcher David Hungerford peered down a microscope at an abnormally small chromosome. In 1990, this ‘Philadelphia chromosome’ was found to cause the swiftly fatal chronic myeloid leukaemia. As science writer Jessica Wapner reveals in this taut, elegant study, a cascade of breakthroughs then led to success with targeted drug Gleevec, a tyrosine kinase inhibitor—and hopes for the cancer-busting potential of rational drug design in general.”
Nature

“[T]he way Wapner repeatedly adds up preceding steps to build to the scientific breakthrough is masterful, making for compulsive, surprisingly emotional reading."
The Scientist

“A thriller with a dash of history.”—Science

“In this meticulously detailed chronicle, science writer Wapner recaps the remarkable development of Gleevec, a cutting-edge drug capable of beating the typically fatal cancer of white blood cells known as chronic myeloid leukemia (CML). . . .Her gracefully written history skillfully combines both the science and humanity of this fascinating search for a cure for CML.”
Publishers Weekly

“Wapner weaves together the basic and applied science with the stories of the dedicated researchers, the broader supporting superstructure of modern medicine and the process of bringing pharmaceuticals to market. . . . An absorbing, complex medical detective story.”
Kirkus Reviews

“Expounding the well-known link between genetics and cancer, this scientific history recounts the initial discovery of a gene mutation that eventually led to enormous breakthroughs in the fight against leukemia.”
The Barnes & Noble Review

“Jessica Wapner reveals how the discovery of a single mutated chromosome led to a trailblazing treatment for leukemia and a variety of other cancers.”
Shelf Awareness

“Splendidly written in the tradition of the legendary medical book, Microbe Hunters, this book proves that medical science is as cool as those forensic shows like CSI.”
Philadelphia Weekly

“I would enthusiastically recommend [this book] to the lay public, people living with cancer and cancer researchers. . . .[T]he story of the Philadelphia chromosome—the scientific creativity and the dedication it celebrates and the medical scientific triumph it represents—is one that deserves to be cherished for eternity.”
Nature Medicine

“[The Philadelphia Chromosome] opens our eyes to a future in which remedies will kill tumors at their root.”
—Philadelphia Inquirer

“[C]hronicles the decades-long quest to develop a targeted, or ‘rational,’ treatment that would attack cancer on the genetic level.”
New York Post

“I enjoyed the book immensely for its enthusiasm, compassion, and depth, while remaining accessible to those not versed in science. It should become a classic.”
Helen Lawce, Journal of the Association of Genetic Technologists

“The story of the Philadelphia chromosome is truly the story of modern cancer biology—from the very earliest description of a chromosomal abnormality in cancer cells to the development of a targeted medicine against a formerly lethal type of leukemia. Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
Siddhartha Mukherjee, Pulitzer Prize–winning author of The Emperor of All Maladies

“Jessica Wapner shows us in The Philadelphia Chromosome how the past and the future combine to dramatically change the course of a disease. This beautifully written book is a blueprint for broader healthcare change. A pivotal book.”
David B. Agus, MD, Professor of Medicine and Engineering, University of Southern California, and author of The End of Illness

“Jessica Wapner has done two kinds of hard work gracefully: the hard work of understanding cancer genetics and the hard work of rendering that subject into human narrative, lucid explanation, and metaphor. The Philadelphia Chromosome is not just an urgently useful book. It's also an elegant one, put together like a Swiss watch.”
David Quammen, author of Spillover: Animal Infections and the Next Human Pandemic

“The Philadelphia Chromosome clearly explains how a half-century’s worth of research transformed a viciously lethal form of cancer into a chronic, treatable condition. Jessica Wapner’s meticulously researched book is both a real-life medical thriller and an engaging narrative about the history of modern cancer research.”
Seth Mnookin, author of The Panic Virus: The True Story Behind the Vaccine-Autism Controversy

Publishers Weekly
In this meticulously detailed chronicle, science writer Wapner recaps the remarkable development of Gleevec, a cutting-edge drug capable of beating the typically fatal cancer of white blood cells known as chronic myeloid leukemia (CML). But the story of Gleevec’s progress also illuminates how a “minute chromosome”—discovered in Philadelphia in 1959—led scientists on a journey to the genetic roots of cancer and “the modern era of personalized medicine.” Gleevec’s triumph—a 2012 study conducted of patients who had taken the drug 10 years ago showed a 68% survival rate—ultimately overcame the daunting unwillingness of Big Pharma and oncologists to accept a lab-synthesized “molecularly targeted medicine.” “In eighteen years,” Wapner writes, “a vision had been wrestled into reality.” Her gracefully written history skillfully combines both the science and humanity of this fascinating search for a cure for CML, including the heartbreaks of Gleevec-pioneering M.D. Brian Druker, thwarted efforts to get the drug into trials, jealousies between scientists, the love story of a reporter and Druker, and the compelling accounts of the patients themselves, who bravely tested the drug and ultimately reclaimed their lives. 8-page photo insert. Agent: Russell Galen, Scovil Galen Ghosh Literary Agency. (May 13)
Library Journal
Freelance science writer Wapner has created a well-rounded work about the discovery of the Philadelphia chromosome, the causes of chronic myeloid leukemia (CML), and the development of the drug Gleevec to treat CML. Wapner does an excellent job of describing the many stages of basic, nonhuman, nonclinical research needed (some of which at first seemed to have no connection with the disease) that led to the knowledge necessary to treat CML. The book also illuminates the process of drug development and the tug of war between caution about side effects and the desire to cure cancer. The story also calls into question regulations that inhibit some industry/academic collaborations. VERDICT A refreshingly balanced view of the topic compared to the one-sided optimism found in Daniel Vasella and Robert Slater's Magic Cancer Bullet (2003). An excellent book for those who want to learn more about how medical discoveries are made and those interested in recent medical history, as well as those whose lives are affected by CML.—Margaret Henderson, Midlothian, VA
Kirkus Reviews
Science writer Wapner uses the development of a successful cure for a once-fatal form of leukemia to illustrate the application of genetic engineering to the frontiers of current medical practice. The discovery of the structure of DNA unleashed the potential to use genetically engineered pharmaceuticals in the treatment of cancer. It took longer than the succeeding 10 years for phrases like "genetic mutation" and "chromosomal abnormality" to become part of the scientific vernacular. By 1959, when the available investigative tools were still primitive by today's standards, a researcher at the University of Pennsylvania discovered an abnormality in the relative sizes of two chromosomes. Ultimately, this led to an understanding of the role of oncogenes, but first a marriage had to take place. The prevailing theory, based on the study of chicken tumors, was that since cancers were contagious, they were caused by viral infection. After virologists determined the genetic makeup of viruses, they opened a second trajectory for the research. They made the remarkable discovery that a normal, proto-oncogenetic chicken gene was temporarily assimilated into an "infecting" virus where it mutated. Normally, the proto-oncogenes were also found in healthy humans, as well as chickens and other animals. Now that the gene was identified, a similar process was discovered in the Philadelphia Chromosome. In this case, a mutated oncogene was located at the point where two specific chromosomes split and interchanged positions before their parts were rejoined. The next problem was to establish the gene's role in normal cell regulation and how to block its functioning after it had mutated. Wapner weaves together the basic and applied science with the stories of the dedicated researchers, the broader supporting superstructure of modern medicine and the process of bringing pharmaceuticals to market. An absorbing, complex medical detective story.

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Product Details

ISBN-13:
9781615191970
Publisher:
Experiment, The
Publication date:
04/08/2014
Edition description:
Reprint
Pages:
344
Sales rank:
130,252
Product dimensions:
5.40(w) x 8.10(h) x 1.10(d)

What People are saying about this

Siddhartha Mukherfee
“The story of the Philadelphia chromosome is truly the story of modern cancer biology. . . . Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
—Siddhartha Mukherjee, Pulitzer Prize-winning author of The Emperor of all Maladies

From the Publisher
“The story of the Philadelphia chromosome is truly the story of modern cancer biology—from the very earliest description of a chromosomal abnormality in cancer cells to the development of a targeted medicine against a formerly lethal type of leukemia. Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
—Siddhartha Mukherjee, Pulitzer Prize–winning author of The Emperor of All Maladies

“Jessica Wapner shows us in The Philadelphia Chromosome how the past and the future combine to dramatically change the course of a disease. This beautifully written book is a blueprint for broader healthcare change. A pivotal book.”
—David B. Agus, MD, Professor of Medicine and Engineering, University of Southern California, and author of The End of Illness

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